Nobuhiko Oridate

Risk factors for post-tonsillectomy hemorrhage.

OBJECTIVEnThe aim of the present study was to investigate the rate of post-tonsillectomy hemorrhage (PTH) in a single institution and to evaluate the clinical risk factors for PTH.nnnMETHODSnWe reviewed the records of 692 patients who underwent tonsillectomy (TE) at Yokohama Minami Kyosai Hospital in Japan. PTH grades were grouped into three categories according to the severity of the hemorrhagic episode: (I) minimal hemorrhage that stopped after noninvasive treatment, (II) hemorrhage requiring treatment with local anesthesia, and (III) hemorrhage requiring reoperation under general anesthesia in the operating room. Clinical risk factors such as sex, age (adults vs. children), TE indication, surgeons skill level, operative time, ligature type, and duration of antibiotic administration for PTH were investigated.nnnRESULTSnAmong the 692 patients, 80 (11.6%) showed PTH, with primary and secondary hemorrhage accounting for 1.6% and 10.0%, respectively. A category III PTH was observed in 18 patients; thus, the overall risk of reoperation was 2.6%. The PTH episode most frequently occurred on postoperative days 5 and 6. The frequency of PTH was significantly higher in male patients and in adults (P<0.01, for both factors). Surgeons skill was also associated with PTH rate. A stepwise multivariate logistic regression revealed that adult age (odds ratio [OR]=18.9) and male gender (OR=3.78) were the clinical risk factors for PTH. It also revealed that male gender (OR=82065335), adult age (OR=10.6), and surgeons skill level (OR=7.50) were the clinical risk factors for the category III PTH.nnnCONCLUSIONSnThe risk of PTH was higher in this report compared with previous reports, which may be associated with the definition of PTH. Clinical risk factors for PTH were adult age and male gender. The surgeons skill level was an additional risk factor for category III PTH.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the hypopharynx treated with concurrent chemoradiotherapy

PurposeThe purpose of the study is to review our experience with concurrent chemoradiotherapy (CCRT) for patients with advanced resectable squamous cell carcinoma (SCC) of the hypopharynx and to evaluate the factors affecting survival and larynx preservation.Study designRetrospective study.Methods and materialsThe records of 102 patients with Stage III or IV resectable SCC of the hypopharynx treated with CCRT between January 1998 and August 2010 were reviewed. Of the 102 patients, 62 were treated with high-dose regimens including cisplatin, 5-fluorouracil, methotrexate, leucovorin or docetaxel, cisplatin, and 5-fluorouracil. The remaining 40 were treated with low-dose regimens including carboplatin and uracil-tegafur, weekly docetaxel, or S-1. Radiotherapy was delivered 5xa0days a week using a single daily fraction of 1.8–2.0 Gray (Gy), to a total dose of 64.8–70.2xa0Gy. Overall survival (OS), disease-specific survival (DSS), and DSS with larynx preservation were estimated using Kaplan–Meier methods. The log-rank test and Cox proportional hazards regression were used to identify significant prognostic factors for OS, DSS, and DSS with larynx preservation.ResultsThe 5-year OS and DSS for all patients treated with CCRT were 51.3 and 64.3xa0%, respectively. The 5-year DSS with larynx preservation was 55.5xa0%. On multivariate analysis, the content of chemotherapy was a significant predictor of OS and DSS for patients undergoing CCRT; N stage was a significant prognostic factor for DSS and larynx preservation.ConclusionThe treatment method including the indication for CCRT may be determined by the contents of the chemotherapy and the N stages of SCC of the hypopharynx.

The molecular mechanism of human papillomavirus-induced carcinogenesis in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Recently, the incidence of oropharyngeal cancer (OPC) has increased markedly in comparison to that of HNSCC, which is associated with the use of tobacco or alcohol or both. This increase has resulted mainly from the global rise in the number of human papillomavirus (HPV)-related oropharyngeal cancers (HPV-OPCs). HPV-OPC has several unique characteristics, including presentation in younger patients, better response rates to treatment, and better prognosis compared to alcohol- and smoking-related HNSCC. HPV infection status is now an independent prognostic factor for survival in patients with OPC. In general, HPV oncoproteins E6 and E7 are the primary viral factors responsible for the initiation and progression of HPV-related cancers via the inactivation of p53 and pRb. However, alterations in additional factors, including genomic instability, HPV DNA integration, and epigenetic alterations, could be equally important for neoplastic transformation and tumor progression. The impact of genomic instability and external environmental factors on the initiation of cervical cancer development through high-risk HPV infection has been well characterized, although less is known about the mechanism underlying HPV-induced carcinogenesis in HNSCC. This review provides an overview of the biology and molecular mechanisms of HPV-related cancers, including a particular focus on several recent studies on the comprehensive characterization of genomic alterations in HPV-associated HNSCC.

Predictive and Prognostic Value of Metabolic Tumor Volume (MTV) in Patients with Laryngeal Carcinoma Treated by Radiotherapy (RT) / Concurrent Chemoradiotherapy (CCRT)

Purpose To evaluate the predictive and prognostic value of pretreatment metabolic tumor volume (MTV) in patients with treated by radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Methods We reviewed the records of 118 patients with newly diagnosed laryngeal carcinoma, who had been treated by RT or CCRT. Pretreatment positron emission tomography (PET) was performed, and MTV values were obtained by contouring margins of standardized uptake value. Clinical factors and MTV were analyzed for their association with survival. Results Patients with residual disease showed a significantly higher MTV than those with a complete response (CR) after primary treatment. Univariate analysis showed that the patients with a high MTV had a significantly lower disease-free survival (DFS) (p < 0.001). Subsite (p = 0.010), T-stage (p < 0.001), nodal metastasis (p < 0.001) and clinical stage (p < 0.001) also correlated significantly with DFS. In the multivariate analysis, MTV and clinical stage were both found to be independent prognostic factors for DFS (p = 0.001, p = 0.034, respectively). The 3-year DFS for patients with a high MTV were significantly poorer than those with a low MTV (p < 0.001). Conclusions MTV of the primary tumor is a significant prognostic factor for DFS in patients with laryngeal carcinoma treated by RT or CCRT. The results imply that MTV could be an important factor when planning treatment and follow-up for patients with laryngeal carcinoma.

Temporary facial nerve dysfunction after parotidectomy correlates with tumor location

OBJECTIVEnTo investigate the clinical factors associated with temporary facial nerve dysfunction (TFND) following surgery for benign parotid gland tumors.nnnMETHODSnWe reviewed the records of 175 patients with benign parotid gland tumors who underwent partial parotidectomy at Yokohama City University Medical Center in Japan. TFND was found in 33 patients (18.9%). We used two hypothetical lines in magnetic resonance imaging (MRI) images to define the tumor location (upper/lower or anterior/posterior) in the parotid gland. We then studied the associations of TFND with the following clinical factors: patient age, tumor size, histopathological diagnosis, and the location of the tumor within the parotid gland (superficial lobe/deep lobe; upper part/lower part; and anterior part/posterior part).nnnRESULTSnTumors located in the upper parts, anterior parts or the deep lobes of the parotid gland had statistically higher incidences of TFND compared with tumors located in the lower parts, posterior parts or the superficial lobe (P<0.001, <0.001, <0.01, respectively). The odds ratio for the risk of TFND was significantly high if tumors were located in the upper parts, the anterior parts or the deep lobes with stepwise multivariate regression analysis. The other factors, including patients age, tumor size, histopathology of the tumor, and inadequate surgeons experience, were not apparent risks for TFND.nnnCONCLUSIONSnParotid gland tumors located in the upper parts, the anterior parts or the deep lobes had a higher risk of TFND. The two hypothetical lines we used were shown to be useful to define the tumor location, eventually the risk of TFND.

Predictive Significance of Tumor Depth and Budding for Late Lymph Node Metastases in Patients with Clinical N0 Early Oral Tongue Carcinoma

In clinical N0 early oral tongue carcinoma, treatment of occult lymph node metastasis is controversial. The purpose of this study was to assess the histopathological risk factors for predicting late lymph node metastasis in early oral tongue carcinoma. We retrospectively reviewed 48 patients with early oral tongue squamous cell carcinoma. Associations between the histopathological factors (depth of tumor, differentiation, blood vessel invasion, lymphatic invasion, and tumor budding) and late lymph metastasis were analyzed. Although the univariate analysis identified blood vessel invasion, lymphatic invasion, and high-grade tumor budding as predictive factors for neck recurrence (pu2009<u20090.001), the Cox proportional hazards model identified high-grade tumor budding as an independent predictive factor (pu2009<u20090.01). The combination of a tumor depthu2009≥u20093xa0mm and high-grade tumor budding yielded high diagnostic accuracy. Tumor depth and budding grade were identified as histopathological risk factors for late neck recurrence in clinical N0 early oral tongue carcinoma.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the head and neck treated with salvage surgery after concurrent chemoradiotherapy

BackgroundFor primary organ preservation, concurrent chemoradiotherapy (CCRT) is performed for advanced squamous cell carcinoma of the head and neck (SCCHN). In this organ-preservation setting with CCRT, surgery is reserved as a salvage treatment in cases of locoregional failure after CCRT. The purpose of the study was to review our experience with salvage surgery after CCRT for patients with SCCHN and to evaluate the effectiveness and prognostic factors affecting survival.MethodsThe records of patients with stage II-IVB SCC of the larynx, oropharynx, or hypopharynx treated with salvage surgery after CCRT between 1998 and 2012 were reviewed.ResultsA total of 645 patients with previously untreated, resectable SCC of the larynx, oropharynx, or hypopharynx received CCRT. Salvage surgery was performed for 78 of 225 patients with residual or recurrent tumors. The 5-year overall survival (OS) and disease-specific survival rates for patients who received salvage surgery were 61.0 and 65.5xa0%, respectively. Stage IV, poorly differentiated, synchronous double cancer, and surgical complications were significant predictors of unfavorable OS on multivariate analysis. Postoperative complications were observed in 30 patients (38.5xa0%).ConclusionsSalvage surgery is the best therapeutic option for failure after CCRT for SCCHN because of its good survival rate, although a high surgical complication rate is seen. Patients with initial stage IV tumors, poorly differentiated SCC, or synchronous double cancer are considered for further adjuvant treatment.

Identification of human papillomavirus (HPV) 16 DNA integration and the ensuing patterns of methylation in HPV-associated head and neck squamous cell carcinoma cell lines

Recent studies showed that human papillomavirus (HPV) integration contributes to the genomic instability seen in HPV‐associated head and neck squamous cell carcinoma (HPV‐HNSCC). However, the epigenetic alterations induced after HPV integration remains unclear. To identify the molecular details of HPV16 DNA integration and the ensuing patterns of methylation in HNSCC, we performed next‐generation sequencing using a target‐enrichment method for the effective identification of HPV16 integration breakpoints as well as the characterization of genomic sequences adjacent to HPV16 integration breakpoints with three HPV16‐related HNSCC cell lines. The DNA methylation levels of the integrated HPV16 genome and that of the adjacent human genome were also analyzed by bisulfite pyrosequencing. We found various integration loci, including novel integration sites. Integration loci were located predominantly in the intergenic region, with a significant enrichment of the microhomologous sequences between the human and HPV16 genomes at the integration breakpoints. Furthermore, various levels of methylation within both the human genome and the integrated HPV genome at the integration breakpoints in each integrant were observed. Allele‐specific methylation analysis suggested that the HPV16 integrants remained hypomethylated when the flanking host genome was hypomethylated. After integration into highly methylated human genome regions, however, the HPV16 DNA became methylated. In conclusion, we found novel integration sites and methylation patterns in HPV‐HNSCC using our unique method. These findings may provide insights into understanding of viral integration mechanism and virus‐associated carcinogenesis of HPV‐HNSCC.

An effective screening strategy for deafness in combination with a next-generation sequencing platform: a consecutive analysis

The diagnosis of the genetic etiology of deafness contributes to the clinical management of patients. We performed the following four genetic tests in three stages for 52 consecutive deafness subjects in one facility. We used the Invader assay for 46 mutations in 13 genes and Sanger sequencing for the GJB2 gene or SLC26A4 gene in the first-stage test, the TaqMan genotyping assay in the second-stage test and targeted exon sequencing using massively parallel DNA sequencing in the third-stage test. Overall, we identified the genetic cause in 40% (21/52) of patients. The diagnostic rates of autosomal dominant, autosomal recessive and sporadic cases were 50%, 60% and 34%, respectively. When the sporadic cases with congenital and severe hearing loss were selected, the diagnostic rate rose to 48%. The combination approach using these genetic tests appears to be useful as a diagnostic tool for deafness patients. We recommended that genetic testing for the screening of common mutations in deafness genes using the Invader assay or TaqMan genotyping assay be performed as the initial evaluation. For the remaining undiagnosed cases, targeted exon sequencing using massively parallel DNA sequencing is clinically and economically beneficial.

Novel PTPRQ mutations identified in three congenital hearing loss patients with various types of hearing loss

Objectives: We present 3 patients with congenital sensorineural hearing loss (SNHL) caused by novel PTPRQ mutations, including clinical manifestations and phenotypic features. Methods: Two hundred twenty (220) Japanese subjects with SNHL from unrelated and nonconsanguineous families were enrolled in the study. Targeted genomic enrichment with massively parallel DNA sequencing of all known nonsyndromic hearing loss genes was performed to identify the genetic cause of hearing loss. Results: Four novel causative PTPRQ mutations were identified in 3 cases. Case 1 had progressive profound SNHL with a homozygous nonsense mutation. Case 2 had nonprogressive profound SNHL with a compound heterozygous mutation (nonsense and missense mutation). Case 3 had nonprogressive moderate SNHL with a compound heterozygous mutation (missense and splice site mutation). Caloric test and vestibular evoked myogenic potential (VEMP) test showed vestibular dysfunction in Case 1. Conclusion: Hearing loss levels and progression among the present cases were varied, and there seem to be no obvious correlations between genotypes and the phenotypic features of their hearing loss. The PTPRQ mutations appeared to be responsible for vestibular dysfunction.